Marchetti A, Buttitta F, Merlo G, Diella F, Pellegrini S, Pepe S, Macchiarini P, Chella A, Angeletti C A, Callahan R
Institute of Pathological Anatomy and Histology, University of Pisa, Italy.
Cancer Res. 1993 Jun 15;53(12):2846-51.
Alterations of p53 are one of the most common molecular changes found in all types of lung tumors, suggesting a crucial role for p53 in bronchial carcinogenesis. However, the prognostic significance of p53 abnormalities in lung cancer patients is still unclear. By using genetic and immunohistochemical methods we have found p53 alterations in 40 of 53 (75%) primary, resected non-small cell lung cancer. A strong association (P = 0.0015) was found between deletions on chromosome region 17p13.3 and p53 mutations suggesting that loss of the wild-type p53 allele might be necessary for tumorigenesis. Correlations to clinicopathological parameters showed that p53 alterations (structural aberration of the gene and/or nuclear accumulation of the protein) are significantly linked with metastatic involvement of hilar and mediastinal lymph nodes (P < 0.01). Since the latter are well established prognostic factors for non-small cell lung cancer, p53 aberrations may also be a predictor of tumor aggressiveness.
p53基因改变是在所有类型的肺肿瘤中发现的最常见分子变化之一,这表明p53在支气管癌发生过程中起关键作用。然而,p53异常在肺癌患者中的预后意义仍不清楚。通过基因和免疫组化方法,我们在53例原发性、已切除的非小细胞肺癌中有40例(75%)发现了p53基因改变。在染色体区域17p13.3的缺失与p53突变之间发现了强关联(P = 0.0015),这表明野生型p53等位基因的缺失可能是肿瘤发生所必需的。与临床病理参数的相关性表明,p53改变(基因的结构畸变和/或蛋白质的核内积聚)与肺门和纵隔淋巴结的转移受累显著相关(P < 0.01)。由于后者是公认的非小细胞肺癌预后因素,p53畸变也可能是肿瘤侵袭性的一个预测指标。